Table 2.

Immune responses in seronegative participants

	Total (n=133)		Two doses of ChAdOx1 nCoV-19 plus one dose of BNT162b2 (n=69)		Three doses of BNT162b2 (n=64)
	Full-dose BNT162b2 (n=66)	Half-dose mRNA-1273 (n=67)	Full-dose BNT162b2 (n=35)	Half-dose mRNA-1273 (n=34)	Full-dose BNT162b2 (n=31)	Half-dose mRNA-1273 (n=33)
SARS-CoV-2 anti-spike protein IgG concentration, ELU/mL
Day 28 after the third dose	23 325 (20 030–27 162); 66	25 317 (20 996–30 528); 66	20 502 (16 473–25 517); 35	21 980 (16 476–29 324); 33	26 982 (22 056–33 008); 31	29 161 (23 093–36 823); 33
Day 0 of fourth dose	3049 (2550–3646); 66	3469 (2730–4407); 66	2532 (1974–3247); 35	2571 (1874–3527); 34	3761 (2959–4780); 31	4769 (3421–6648); 32
Day 14 after the fourth dose	37 460 (31 996–43 857); 65	54 936 (46 826–64 452); 67	33 316 (26 942–41 198); 35	52 080 (41 163–65 894); 34	42 949 (34 148–54 019); 30	58 043 (46 693–72 150); 33
Fold change (day 14 after fourth dose vs day 28 after third dose)	1·59 (1·41–1·78); 65	2·19 (1·90–2·52); 66	1·62 (1·35–1·95); 35	2·41 (1·90–3·05); 33	1·54 (1·35–1·76); 30	1·99 (1·71–2·31); 33
Fold change (day 14 after fourth dose vs day 0 of fourth dose)	12·19 (10·37–14·32); 65	15·90 (12·92–19·58); 66	13·16 (10·24–16·91); 35	20·26 (15·09–27·21); 34	11·14 (9·21–13·47); 30	12·30 (9·39–16·11); 32
Cellular response (wild-type), spot forming cells per 106 PBMCs*
Day 28 after the third dose	96·03 (65·68–140·42; 35	111·19 (75·87–162·95); 33	133·33 (81·31–218·62); 19	113·40 (57·93–221·98); 17	65·04 (37·76–112·03); 16	108·90 (75·81–156·43); 16
Day 0 of fourth dose	19·32 (10·99–33·97);36	35·32 (20·66–60·40); 34	18·85 (8·31–42·77); 20	42·13 (18·58–95·51); 16	19·93 (9·14–43·48); 16	30·20 (14·71–62·02); 18
Day 14 after the fourth dose	112·64 (80·61–157·38); 20	236·95 (146·04–384·48); 20	141·99 (92·57–217·80); 11	232·98 (116·70–465·12); 11	84·87 (51·94–138·66); 9	241·91 (118·79–492·64); 9
Fold change (day 14 after fourth dose vs day 28 after third dose)	1·10 (0·72–1·70); 18	1·69 (1·22–2·34); 19	1·09 (0·63–1·89); 10	1·16 (0·79–1·70); 11	1·12 (0·54–2·31); 8	2·83 (2·02–3·96); 8
Fold change (day 14 after fourth dose vs day 0 of fourth dose)	7·32 (3·24–16·54); 19	6·22 (3·90–9·92); 20	11·07 (4·21–29·12); 11	6·34 (2·89–13·92); 11	4·14 (1·04–16·54); 8	6·08 (3·86–9·56); 9
Cellular response (beta), spot forming cells per 106 PBMCs*
Day 28 after the third dose	98·34 (72·11–134·10); 35	108·85 (76·90–154·07); 33	132·70 (87·79–200·59); 19	120·52 (65·57–221·54); 17	68·89 (45·39–104·57); 16	97·69 (70·62–135·12); 16
Day 0 of fourth dose	18·53 (10·60–32·37); 36	28·35 (15·40–52·19); 34	16·71 (7·50–37·22); 20	37·69 (16·24–87·46); 16	21·07 (9·64–46·06); n=16	22·01 (9·11–53·20); 18
Day 14 after the fourth dose	85·55 (54·11–135·28); 20	245·84 (158·84–380·50); 20	96·25 (55·85–165·86); 11	256·42 (142·42–461·65); 11	74·08 (33·34–164·60); 9	233·50 (117·10–465·64); 9
Fold change (day 14 after fourth dose vs day 28 after third dose)	0·98 (0·64–1·50); 18	1·96 (1·36–2·82); 19	0·93 (0·54–1·61); 10	1·30 (0·91–1·87); 11	1·03 (0·50–2·12); 8	3·45 (2·10–5·69); 8
Fold change (day 14 after fourth dose vs day 0 of fourth dose)	5·47 (2·30–13·02); 19	8·48 (4·72–15·22); 20	7·63 (2·51–23·17); 11	8·98 (4·19–19·23); 11	3·46 (0·85–14·08); 8	7·91 (3·04–20·56); 9
Cellular response (delta), spot forming cells per 106 PBMCs*
Day 28 after the third dose	92·48 (66·90–127·85); 35	104·34 (72·95–149·24); 33	130·31 (92·00–184·58); 19	114·49 (61·51–213·11); 17	61·55 (36·64–103·38); 16	94·54 (66·74–133·91); 16
Day 0 of fourth dose	16·40 (9·38–28·68); 36	35·93 (20·29–63·62); 34	18·39 (8·68–38·95); 20	41·93 (17·99–97·78); 16	14·22 (6·02–33·58); 16	31·31 (14·19–69·08); 18
Day 14 after the fourth dose	94·20 (66·92–132·60); 20	239·62 (155·19–369·97); 20	108·24 (69·20–169·28); 11	244·67 (141·79–422·20); 11	79·49 (46·55–135·72); 9	233·59 (111·99–487·24); 9
Fold change (day 14 after fourth dose vs day 28 after third dose)	1·00 (0·68–1·49); 18	2·03 (1·39–2·97); 19	0·88 (0·56–1·38); 10	1·28 (0·89–1·84); 11	1·19 (0·59–2·40); 8	3·85 (2·39–6·21); 8
Fold change (day 14 after fourth dose vs day 0 of fourth dose)	7·57 (3·32–17·25); 19	6·35 (3·51–11·49); 20	9·37 (3·56–24·67); 11	6·62 (2·87–15·25); 11	5·64 (1·27–25·06); 8	6·04 (2·48–14·68); 9

Data are geometric mean (95% CI); number of participants contributing to analysis. ELU=ELISA laboratory units. PBMCs=peripheral blood mononuclear cells.

^*Due to logistical reasons, only 50% of study sites collected cellular immunology samples (proximity to external laboratory) in the main COV-BOOST study; the cellular immunology samples after the fourth dose were collected in the immunology cohort.